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Antineoplásicos , Leucemia Mieloide de Fase Crónica , Piridazinas , Antineoplásicos/uso terapéutico , Dasatinib/uso terapéutico , Humanos , Imidazoles , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridazinas/uso terapéuticoRESUMEN
The prognosis of several lymphoid malignancies has improved through development of novel therapies, combination with traditional chemotherapies, and delineation of appropriate therapeutic sequencing. Toxicities that are arising because of prolonged or multiple sequential therapeutic interventions are becoming increasingly impactful. Among the broad spectrum of complications that patients with lymphoid malignancies may experience, cardiovascular toxicities are significant in terms of morbidity and mortality. The entire cardiovascular system can be affected, but cardiomyopathy, heart failure, and arrhythmias remain of greatest concerns with the use of anthracyclines, hematopoietic stem cell transplantation, and radiation therapy in patients with lymphoid malignancies. These aspects will be covered in this article within the framework of case-based discussions. Key to the management of cardiovascular complications in patients with lymphoid malignancies is awareness and preparedness across the cancer continuum. Baseline risk stratification helps to direct surveillance and early intervention efforts before, during, and after cancer therapy, which are paramount for the best possible outcomes. Along these lines, the overall goal is to enable the best possible therapies for lymphoid malignancies without the complications of clinically significant cardiovascular events.
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Cardiomiopatías , Cardiopatías , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Antraciclinas/efectos adversos , Cardiomiopatías/etiología , Cardiopatías/inducido químicamente , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
PURPOSE: To evaluate the prevalence of burnout among hematology-oncology pharmacists and factors associated with an increased risk of high burnout. METHODS: Between October and November 2020, members of the Hematology/Oncology Pharmacy Association were invited to complete an anonymous survey. Questions included the Maslach Burnout Inventory (MBI), Well-Being Index, and sociodemographic and occupational factors linked with burnout. RESULTS: Of 3,024 pharmacists contacted, 614 pharmacists (20.3%) responded to an online survey and 550 (18.2% of overall sample) completed the MBI and were included for analysis. Overall, high levels of burnout were observed in 61.8% of respondents based on the MBI, with 57.9% of respondents scoring high on the emotional exhaustion domain and 31.3% high in the depersonalization domain. Pharmacists with burnout worked on average 48.6 (±9.6) hours per week compared with 44.5 (±9.6) hours per week for those without high burnout and spent more time on administrative tasks per week (7.5 hours v 4.3 hours; all P < .001). Pharmacists reporting high burnout were more likely to report concern they had made a major medication error within the past 3 months (27.6% v 8.1%; P < .001) and greater intent to leave their current job within 2 years (60.3% v 19.0%; P < .001). CONCLUSION: Burnout is prevalent among hematology-oncology pharmacists and may affect both patient safety and the adequacy of the workforce. Risk factors for burnout among hematology-oncology pharmacists in this study may be targets for burnout mitigation and prevention strategies to reduce the impact on pharmacists and improve cancer care for patients.
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Agotamiento Profesional , Hematología , Agotamiento Profesional/epidemiología , Agotamiento Psicológico , Humanos , Satisfacción en el Trabajo , Farmacéuticos/psicologíaRESUMEN
INTRODUCTION: Acute kidney injury (AKI) affects 30% of adults hospitalized with hematologic malignancy. Little is known about the long-term impact on kidney outcomes in this population despite the close relationship between kidney function and malignancy treatment eligibility. The purpose of this population-based cohort study was to determine the effect of AKI on kidney function in the year following a new diagnosis of acute leukemia or lymphoma. METHODS: Participants were adults hospitalized within 3 weeks of malignancy diagnosis. Baseline kidney function was determined and AKI diagnosed using standardized criteria. Cox proportional hazard modeling examined the relationship between AKI and a ≥30% decline in estimated glomerular filtration rate (eGFR) from baseline in the 1 year following hospitalization as the primary endpoint. RESULTS: AKI occurred in 33% of 1064 participants, with 70% of episodes occurring within 48 hours of hospitalization, and significantly increased risk for a ≥ 30% decline in eGFR (hazard ratio [HR] 2.7, 95% confidence interval [CI] 2.2-3.5) and incident chronic kidney disease (HR 2.2, 95% CI 1.7-2.8). AKI remained a significant predictor of eGFR decline in subgroup and multivariable analyses (adjusted HR 1.9, 95% CI 1.4-2.7). A ≥ 30% decline in eGFR increased the risk for death within 1 year in participants with AKI (HR 2.1, 95% CI 1.3-3.3). CONCLUSION: Results aid in identifying individuals at highest risk for poor outcomes and highlight the need for research involving interventions that preserve kidney function from the time of initial hospitalization with a hematologic malignancy into the postdischarge period.
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PURPOSE OF REVIEW: For decades, the management of chronic myelomonocytic leukemia (CMML) or juvenile myelomonocytic leukemia (JMML) has been largely inextricable from myelodysplastic syndromes (MDS), myeloproliferative neoplasms, and acute myeloid leukemia. Hallmarks of these diseases have been the emergence of unique genomic signatures and discouraging responses to available therapies. Here, we will critically examine the current options for management and review the rapidly developing opportunities based on advances in CMML and JMML disease biology. RECENT FINDINGS: Few clinical trials have exclusively been done in CMML, and in JMML, the rarity of the disease limits wide scale participation. Recent case series in JMML suggest that hypomethylating agents (HMAs) are a viable option for bridging to curative intent with allogeneic hematopoietic stem cell transplant or as posttransplant maintenance. Emerging evidence has demonstrated targeting the RAS-pathway via MEK inhibition may also be considered. In CMML, treatment with HMAs is largely derived from data inclusive of MDS patients, including a small number of patients with dysplastic CMML variants. Based on CMML disease biology, additional therapeutic targets being investigated include inhibitors of splicing, CD123/dendritic cell axis, inherent GM-CSF progenitor cell hypersensitivity, and targeting the JAK/STAT pathway. Current evidence is also expanding for oral HMAs. The management of CMML and JMML is rapidly evolving and clinicians must be aware of the genetic landscape and expanding treatment options to ensure these rare populations are afforded therapeutic interventions best suited to their needs.
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Leucemia Mieloide/terapia , Leucemia Mielomonocítica Juvenil/terapia , Factores de Edad , Biomarcadores , Terapia Combinada , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/etiología , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/etiología , Leucemia Mielomonocítica Crónica/terapia , Leucemia Mielomonocítica Juvenil/diagnóstico , Leucemia Mielomonocítica Juvenil/etiología , Terapia Molecular DirigidaRESUMEN
The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations. Three hundred and nine consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions. A total of 309 cases were prospectively evaluated. One hundred and forty (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board. A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.
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Linfoma , Neoplasias , Humanos , Comunicación Interdisciplinaria , Linfoma/diagnóstico , Linfoma/terapia , RadiografíaRESUMEN
Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Estudios Transversales , Humanos , Cumplimiento de la Medicación , Pacientes Ambulatorios , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Optimal treatment for myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes remain to be defined and are currently extrapolated from MDS and MPN. The heterogeneity of these diseases and their rare occurrences add to this void. Supportive care therapies such as erythropoiesis stimulating agents, iron chelation and cytoreductive therapy do not have prospective evidence in these disorders and the only approved treatments, hypomethylating agents, are based on the inclusion of a small number of chronic myelomonocytic leukaemia patients in MDS predominant trials. While allogeneic stem cell transplant remains the only curative option, the median age at presentation (7th decade), comorbidities, risk of disease relapse, and transplant related morbidity and mortality, make this option accessible to < 10% of patients. The advent of next generation sequencing has better defined the genomic landscape and opened the doors for personalized medicine. Herein we focus on recent therapeutic advances and options in MDS/MPN overlap syndromes.
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Antineoplásicos/uso terapéutico , Secuenciación de Nucleótidos de Alto Rendimiento , Leucemia Mielógena Crónica BCR-ABL Positiva , Síndromes Mielodisplásicos , Medicina de Precisión , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/terapiaRESUMEN
To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11/2013 to 12/2017. Of 209 patients, 131 (74%) had unmutated IGHV, 38 (20%) had TP53 disruption, and 47 (22%) were previously untreated. A total of 87/209 (42%) patients started reduced dose ibrutinib (<420 mg daily; n = 43, physician preference; n = 33, concomitant medications; and n = 11, other). During 281 person-years of treatment, 91/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow-up of 24 months, the estimated median event-free survival (EFS) was 36 months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P = .006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P = .048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P = .015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.
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Adenina/análogos & derivados , Deprescripciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Piperidinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Adenina/administración & dosificación , Adenina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Piperidinas/uso terapéutico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes in tumor lysis syndrome (TLS), specifically, the prevention of acute kidney injury (AKI). This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS. Excluded patients had AKI or were on dialysis at hospital admission. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. In 383 included patients, the incidence of new-onset AKI during hospitalization was 6%. Predictors included age, history of renal or cardiovascular disease, and UA >8 mg/dL. Rasburicase use did not significantly impact the risk of developing AKI (HR 2.3; p = .11). The UA level at the time of administration did not modify the effect of rasburicase on prevention of AKI (p = .36 for the interaction term).
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Lesión Renal Aguda/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma/tratamiento farmacológico , Síndrome de Lisis Tumoral/epidemiología , Urato Oxidasa/administración & dosificación , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Anciano , Femenino , Humanos , Incidencia , Linfoma/sangre , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Síndrome de Lisis Tumoral/sangre , Síndrome de Lisis Tumoral/etiología , Síndrome de Lisis Tumoral/prevención & control , Ácido Úrico/antagonistas & inhibidores , Ácido Úrico/sangre , Ácido Úrico/toxicidadRESUMEN
PURPOSE: The development, implementation, and evaluation of a pharmacogenomics education program for pharmacists in a large, integrated multicampus health system are described. SUMMARY: Pharmacogenomics has been described as tailoring medications to each patient's unique genetic sequence with the goals of minimizing harmful effects and optimizing therapeutic effects. Pharmacists are uniquely trained to lead the implementation of pharmacogenomics in clinical care. After assessment of pharmacists' comfort with pharmacogenomics, different approaches were explored to develop, pilot test, and disseminate pharmacogenomics education across a multicampus academic medical center. Limited success with large-audience, single-lecture didactic education led to development and delivery of targeted, competency-based online modules using the institution's academic virtual learning environment and course management system. Implementation steps included (1) collaboration with the Mayo Clinic Center for Individualized Medicine to create an interprofessional development team and project charter, (2) galvanizing pharmacy leadership support across multiple campuses, (3) development of competency-based interactive modules, and (4) assessment of the quality of and learner satisfaction with the modules. Significant improvements in competency scores were observed with each module and across the multiple campuses. Satisfaction with the education program was assessed at the end of a 4-module series. CONCLUSION: A pharmacogenomics educational program targeting pharmacists was developed through interprofessional collaboration and provided a novel opportunity to construct an educational infrastructure to support enterprise health-system campuses with limited educational resources.
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Educación Continua en Farmacia/métodos , Farmacogenética/educación , Curriculum , Educación Continua en Farmacia/organización & administración , Humanos , Medicina de Precisión , Desarrollo de Programa , Encuestas y Cuestionarios , Estados UnidosRESUMEN
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class. Additionally, several agents have critically important drug-drug interactions or dose-modification implications in hepatic or renal insufficiency that can be easily overlooked, and exacerbate adverse effects. As treatment of MM moves from fixed-duration traditional chemotherapy to novel agent-based regimens, commonly administered continuously until disease progression or intolerable toxicities, providers must adopt their management strategies for both acute and long-term adverse effects. Early and frequent monitoring for therapy-related complications, dose adjustments when needed, and timely treatment for toxicities are all important steps toward ensuring longevity of treatment from a limited array of therapeutic options that currently exist for a disease with a relapsing and remitting course.
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Antineoplásicos Inmunológicos/efectos adversos , Inhibidores de Histona Desacetilasas/efectos adversos , Factores Inmunológicos/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Inhibidores de Proteasoma/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inhibidores de Proteasoma/uso terapéuticoRESUMEN
The optimal antithrombin(AT) activity parameters for replacement as thromboprophylaxis following asparaginase remains unclear. This single-center, retrospective study evaluated two sets of AT replacement thresholds and targets in adults receiving asparaginase-containing chemotherapy. AT supplementation adhered to institutional standards, which lowered the AT activity target from 100% to 80% in 6/2014. Ninety-two patients were evaluated. Cumulative thrombosis incidence was 16% at 6 months (95%CI:6.8-24.0, maximum follow-up 315 days) with similar incidence between the 80% and 100% target groups, 14% (2 of the 14) and 13% (10 of the 78), respectively, with a small non-Line-Related DVT incidence (3%). Most thrombotic events occurred during induction chemotherapy and demonstrated no associations with replacement target, cumulative days or cumulative area under AT activity target, number of asparaginase doses, or cumulative asparaginase dose. Median estimated AT replacement expenditure was $34,963USD (IQR $16,260USD to $79,319USD) per patient. Cost-effectiveness and optimization of AT replacement for thromboprophylaxis following asparaginase requires prospective evaluation.
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Antitrombinas/uso terapéutico , Asparaginasa/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Trombosis/prevención & control , Adulto , Antitrombinas/economía , Análisis Costo-Beneficio , Estudios de Factibilidad , Femenino , Neoplasias Hematológicas/complicaciones , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/economía , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trombosis/complicacionesRESUMEN
Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A. We evaluated concomitant medication use in 118 ibrutinib-treated CLL patients outside the context of clinical trials. Seventy-five (64%) patients were on medications that could increase ibrutinib toxicity and 4 (3%) were on drugs that could decrease ibrutinib efficacy. Nineteen (16%) patients were on concomitant CYP3A inhibitors (11 moderate, 8 strong), and 4 (3%) were on CYP3A inducers (two patients were on both CYP3A inhibitors and inducers). Although the ibrutinib starting dose was changed in 18 patients on CYP3A interacting medications, no difference in 18-month progression-free survival or rate of ibrutinib discontinuation was observed in patients who were not. In routine clinical practice, 2 of 3 CLL patients commencing ibrutinib are on a concomitant medication with potential to influence ibrutinib metabolism. Formal medication review by a pharmacist should be considered in all patients initiating ibrutinib.
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Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/epidemiología , Farmacovigilancia , Pautas de la Práctica en Medicina , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Biomarcadores , Citocromo P-450 CYP3A/genética , Interacciones Farmacológicas , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Variantes Farmacogenómicas , Piperidinas , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Resultado del TratamientoRESUMEN
Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 µmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.